Genomic instability such as aneuploidies, deletions, amplifications, and translocations, can give rise to growth advantages for an abnormal cell during adaptive evolution. It has been proposed that the instability and fitness advantage associated with these types of genomic rearrangements are important in the early stages of many types of cancer. Similar mechanisms can potentially lead to the establishment of new species during the process of speciation, where genomic rearrangements can potentially yield selective fitness advantage leading to novel genome complements. The mechanisms that lead to genome rearrangements described above and their role during adaptive evolution will be investigated using hybrid organisms of the yeast, Saccharomyces. Specifically, a detailed characterization of the chromosomal rearrangements that occur during speciation of hybrid yeasts will be performed and potential genie incompatibilities between Saccharomyces species will be identified. In addition, the genomic rearrangements and stability of these hybrid yeasts under specific environmental pressures will be investigated. Results from these specific aims will provide insights into the importance of genome rearrangements in adaptive evolution with applicability to the progression of cancer. [unreadable] [unreadable] The progression of cancer has been likened to the process of emergence of new species. Understanding the mechanisms governing how new species are formed and their stability under specific conditions will further our knowledge of the process of speciation. This knowledge can be extended to the progression of cancer, and will thus have potential impact on treatment of the disease. [unreadable] [unreadable] [unreadable]